Local resiniferatoxin induces long-lasting analgesia in a rat model of full thickness thermal injury

Date
2016-10-28
Authors
Salas, Margaux M.
Clifford, John L.
Hayden, Jessica R.
Iadarola, Michael J.
Averitt, Dayna L.
Journal Title
Journal ISSN
Volume Title
Publisher
Oxford University Press
Abstract

Objective Opioid-based analgesics are a major component of the lengthy pain management of burn patients, including military service members, but are problematic due to central nervous system–mediated side effects. Peripheral analgesia via targeted ablation of nociceptive nerve endings that express the transient receptor potential vanilloid channel 1 (TRPV1) may provide an improved approach. We hypothesized that local injection of the TRPV1 agonist resiniferatoxin (RTX) would produce long-lasting analgesia in a rat model of pain associated with burn injury.


Methods Baseline sensitivities to thermal and mechanical stimuli were measured in male and female Sprague-Dawley rats. Under anesthesia, a 100 °C metal probe was placed on the right hind paw for 30 seconds, and sensitivity was reassessed 72 hours following injury. Rats received RTX (0.25 μg/100 μL; ipl) into the injured hind paw, and sensitivity was reassessed across three weeks. Tissues were collected from a separate group of rats at 24 hours and/or one week post-RTX for pathological analyses of the injured hind paw, dorsal spinal cord c-Fos, and primary afferent neuropeptide immunoreactivity.


Results Local RTX reversed burn pain behaviors within 24 hours, which lasted through recovery at three weeks. At one week following RTX, decreased c-Fos and primary afferent neuropeptide immunoreactivities were observed in the dorsal horn, while plantar burn pathology was unaltered.


Conclusions These results indicate that local RTX induces long-lasting analgesia in a rat model of pain associated with burn. While opioids are undesirable in trauma patients due to side effects, RTX may provide valuable long-term, nonopioid analgesia for burn patients.

Description
Article originally published in Pain Medicine, Volume 18, Issue 12, Pages 2453–2465. English. Published online December 2017. https://doi.org/10.1093/pm/pnw260
Keywords
Resiniferatoxin, Burn, Peripheral analgesia, c-Fos, TRPV1, Opioid sparing, Spinal cord, Substance P, CGRP, Opioids
Citation
This is the abstract for an article that is available at: https://doi.org/10.1093/pm/pnw260. Recommended citation: Salas, M. M., Clifford, J. L., Hayden, J. R., Iadarola, M. J., & Averitt, D. L. (2016). Local resiniferatoxin induces long-lasting analgesia in a rat model of full thickness thermal injury. Pain Medicine. This item has been deposited in accordance with publisher copyright and licensing terms and with the author’s permission.
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